The cap structure and the poly(A) tail on messenger RNA (mRNA) work together to stimulate translation initiation in yeast through their interaction with the translation initiation factor eIF4G. The cap binding protein eIF4E and the poly(A) tail binding protein Pab1p mediate the interaction of eIF4G with each of these mRNA structures. The RNA- activated ATPase eIF4A also interacts with eIF4G. This proposal outlines experiments whose goals are to understand how each of these proteins as well as RNA interacts with yeast eIF4G1 and with each other. Another goal is to understand whether eIF4A enzymatic activity or the association of the ribosome bound initiation factor eIF3 with eIF4G1 is stimulated when mRNA is circularized through the interaction of eIF4E and Pab1p with eIF4G1. A final goal of these experiments is to identify and then characterize other yeast proteins which either activate or repress the function of eIF4G1 and its associated proteins. Our results should help to elucidate the mechanisms by which translation initiation is stimulated and regulated in eucaryotes. This information will be invaluable in understanding alterations to the translational apparatus resulting from some types of cellular transformations or viral infections, and in developing assays and then compounds which will provide therapeutic options to correcting these alterations.